Studies on calciferol metabolism. VII. The effects of actinomycin D and cycloheximide on the metabolism, tissue and subcellular localization, and action of vitamin D3.
Studies on calciferol metabolism. VII. The effects of actinomycin D and cycloheximide on the metabolism, tissue and subcellular localization, and action of vitamin D3.
复制标题
骨化醇代谢研究。
DOI：
10.1016/0003-9861(73)90648-6
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发表时间：
1973
影响因子：
3.9
通讯作者：
A. Norman
中科院分区：
文献类型：
--
作者：
H.C. Tsai;R. Midgett;A. Norman
最初假设，主要基于使用放线菌素D的实验，钙化醇（维生素D）通过激活储存在肠道基因组中的信息介导其在肠道中的特征性生理反应。最近的另一种假说认为，放线菌素D通过抑制胆钙化醇向1，25-二羟基胆钙化醇的强制性代谢来阻断对钙化醇的生物反应。本文报道了放线菌素D和放线菌酮对胆钙化醇及其代谢产物25-羟基胆钙化醇和1，25-二羟基胆钙化醇的代谢、亚细胞定位和作用的影响。发现放线菌素D抑制由胆钙化醇或其代谢物刺激的钙转运，而不抑制它们在靶组织（肠粘膜）中的代谢或定位。然而，放线菌素D必须以2小时间隔分4次给药，以阻断1，25-二羟基胆钙化醇对钙转运的刺激。还发现放线菌素D不会降低体外测定的25-羟基胆钙化醇-1-羟化酶的肾脏水平。相反，放线菌酮被发现抑制肠中的甾醇的本地化。此外，放线菌酮降低肾酶水平，这是在体内给药抗生素后在体外测量的。从这些数据可以计算出，25-羟基胆钙化醇-1-羟化酶似乎具有约3小时的t12。因此，这两种抗生素对肠钙转运的抑制实际上可能发生在两个不同的靶器官;放线菌酮通过阻断1，25-二羟基胆钙化醇在肠道内。
It was originally postulated, primarily on the basis of experiments employing actinomycin D, that calciferol (vitamin D) mediated its characteristic physiological responses in the intestine via the activation of information stored in the intestinal genome. A more recent alternative hypothesis suggested that actinomycin D blocked the biological response to calciferol by inhibiting the mandatory metabolism of cholecalciferol to 1, 25-dihydroxycholecalciferol. Presented in this paper are the results of recent experiments studying the effects of both actinomycin D and cycloheximide on the metabolism, subcellular localization, and action of cholecalciferol or its metabolites, 25-hydroxycholecalciferol and 1, 25-dihydroxycholecalciferol. Actinomycin D was found to inhibit calcium transport stimulated by cholecalciferol or its metabolites without inhibiting their metabolism or localization in the target tissue, the intestinal mucosa. However, actinomycin D had to be administered in four doses at 2-hr intervals to block the stimulation of calcium transport by 1, 25-dihydroxycholecalciferol. Actinomycin D was also found not to lower the renal levels of 25-hydroxycholecalciferol-1-hydroxylase, which were measured in vitro. In contrast, cycloheximide was found to inhibit the localization of the sterols in the intestine. Also cycloheximide lowered the renal enzyme levels which were measured in vitro following administration of the antibiotic in vivo. From these data it can be calculated that the 25-hydroxycholecalciferol-1-hydroxylase appears to have a t 1 2 of approximately 3 hr. Thus, the inhibition of intestinal calcium transport by these two antibiotics may in fact occur at two different target organs; cycloheximide by a lowering of the kidney levels of 25-hydroxycholecalciferol-1-hydroxylase and actinomycin D by blocking the action of 1, 25-dihydroxycholecalciferol in the intestine.